Exosomes from Hypoxic Mesenchymal Stem Cells Enhance TGF-β Expression and Promote Collagen Regeneration in Wistar Rats with Collagen Loss

Ade Ifalliah Putri Kusumawardani, Prasetyowati Subchan, Titiek Sumarawati, Eko Setiawan

Abstract


Background: Ultraviolet B (UVB) exposure triggers reactive oxygen species (ROS) formation, inhibits procollagen synthesis via the transforming growth factor-beta (TGF-β)/Smad pathway, and leads to collagen loss. Exosomes derived from hypoxia-conditioned mesenchymal stem cells (EH-MSCs) are more effective than those from normoxic MSCs due to their higher content of miRNAs and cytokines with anti-inflammatory and regenerative properties. This study aims to evaluate the effect of EH-MSC injection on TGF- β levels and collagen density in Wistar male rats with UVB-induced collagen loss. 

Materials and methods: This in vivo experimental study used a post-test only control group design with 30 rats, divided into five groups: Healthy group, 0.9% NaCl-treated group, hyaluronic acid (HA)-treated group, 200μL EH-MSC-treated group, and 300μL EH-MSC-treated group. TGF-β levels were analyzed using ELISA, while collagen density was assessed with Masson trichrome staining.

Results: Highest mean TGF-β levels were observed in the 300μL EH-MSC-treated group (155.56±99.84 pg/mL), while the highest collagen density was found in the Healthy group (23.07±1.81 pg/mL). Mann-Whitney test indicated a significant increase (p=0.008) in TGF-β levels in treatment groups compared to the 0.9% NaCl-treated group. Post Hoc LSD Tamhane test for collagen density also showed a significant increase (p=0.000) in treatment groups compared to the 0.9% NaCl-treated group. 

Conclusion: EH-MSC injection significantly increased TGF-β levels and collagen density, indicating its potential for promoting skin repair in UVB-induced collagen loss.

Keywords: EH-MSC, collagen loss, TGF-β, collagen density 


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References


Ansary TM, Hossain MR, Kamiya K, Komine M, Ohtsuki M. Inflammatory molecules associated with ultraviolet radiation-mediated skin aging. Int J Mol Sci. 2021; 22(8): 3974, CrossRef.

Kartika R, Wibowo H. Impaired function of regulatory t cells in type 2 diabetes mellitus. Mol Cell Biomed Sci. 2020; 4(1): 1-9, CrossRef.

Quan T, He T, Kang S, Voorhees JJ, Fisher GJ. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling. Am J Pathol. 2004; 165(3): 741-51, CrossRef.

Park AY, Lee JO, Jang Y, Kim YJ, Lee JM, Kim SY, et al. Exosomes derived from human dermal fibroblasts protect against UVB‑induced skin photoaging. Int J Mol Med. 2023; 52(6): 120., CrossRef.

Dewiastuti M, Hasanah IF. Pengaruh faktor-faktor risiko penuaan dini di kulit pada remaja wanita usia 18-21 tahun. J Profesi Med J Kedokt dan Kesehat. 2017; 10(1): 21-25, CrossRef.

Sugianto M, Achadiyani A, Nugraha GI. Antioxidant effects of red fruit oil on MMP-1 gene expression and malondialdehyde levels on skin exposed to UVB rays. Mol Cell Biomed Sci. 2019; 3(2): 100-6, CrossRef.

Guo J, Fang W, Wang F. Injectable fillers: Current status, physicochemical properties, function mechanism, and perspectives. RSC Adv. 2023; 13(34): 23841-58, CrossRef.

Valentina I, Achadiyani A, Adi SS, Lesmana R, Farenia R. Effect of Lactobacillus reuteri administration on wrinkle formation and type I procollagen levels in UVB-exposed male Balb/c Mice (Mus musculus). Mol Cell Biomed Sci. 2020; 4(3): 113-20, CrossRef.

Zhao Q, Ren H, Han Z. Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother. 2016; 2(1): 3-20, CrossRef.

Beegle J, Lakatos K, Kalomoiris S, Stewart H, Isseroff RR, Nolta JA, et al. Hypoxic preconditioning of mesenchymal stromal cells induces metabolic changes, enhances survival, and promotes cell retention in vivo. Stem Cells. 2015; 33(6): 1818-28, CrossRef.

Gao W, Wang X, Si Y, Pang J, Liu H, Li S, et al. Exosome derived from ADSCs attenuates ultraviolet B-mediated photoaging in human dermal fibroblasts. Photochem Photobiol. 2021; 97(4): 795-804, CrossRef.

Wu JY, Wu SN, Zhang LP, Zhao XS, Li Y, Yang QY, et al. Stem cell-derived exosomes: A new method for reversing skin aging. Tissue Eng Regen Med. 2022; 19(5): 961-8, CrossRef.

Hu JC, Zheng CX, Sui BD, Liu WJ, Jin Y. Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration. World J Stem Cells. 2022; 14(5): 318-29, CrossRef.

Zhuo H, Chen Y and Zhao G (2024) Advances in application of hypoxia-preconditioned mesenchymal stem cell-derived exosomes. Front. Cell Dev. Biol. 2024; 12: 1446050, CrossRef.

Cai J, Wu J, Wang J, Li Y, Hu X, Luo S, et al. Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential. Cell Biosci. 2020; 10(69): 1-14, CrossRef.

Aheget H, Mazini L, Martin F, Belqat B, Marchal JA, Benabdellah K. Exosomes: Their role in pathogenesis, diagnosis and treatment of diseases. Cancers. 2020; 13(1): 84, CrossRef.

Ke Y, Wang XJ. TGFβ Signaling in Photoaging and UV-Induced Skin Cancer. J Invest Dermatol. 2021; 141(4): 1104-10,

Tienda-Vázquez MA, Hanel JM, Márquez-Arteaga EM, Salgado-Álvarez AP, Scheckhuber CQ, Alanis-Gómez JR, et al. Exosomes: A Promising Strategy for Repair, Regeneration and Treatment of Skin Disorders. Cells. 2023; 12(12): 1625, CrossRef.

Aisyah R, Jatmiko SW. Jalur Sinyal TGF-β Berperan Dalam Self Renewal, Diferensiasi, Dan Proliferasi Stem Cell. Saintika Med. 2019; 15(1): 50-59, CrossRef.

Ha DH, Kim H keun, Lee J, Kwon HH, Park GH, Yang SH, et al. Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells. 2020; 9(5): 1157, CrossRef.

Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2(1): 17023, CrossRef.

Putra A, Pertiwi D, Milla MN, Indrayani UD, Jannah D, Sahariyani M, et al. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Maced J Med Sci. 2019; 7(3): 305-10, CrossRef.

Gentile P, Scioli MG, Bielli A, De Angelis B, De Sio C, De Fazio D, et al. Platelet-rich plasma and micrografts enriched with autologous human follicle mesenchymal stem cells improve hair re-growth in androgenetic alopecia. Biomolecular Pathway Analysis and Clinical Evaluation. Biomedicines. 2019; 7(2): 27, CrossRef.

MacLeod AS, Mansbridge JN. The innate immune system in acute and chronic wounds. Adv Wound Care. 2016; 5(2): 65-78, CrossRef.

de Jong OG, van Balkom BW, Gremmels H, Verhaar MC. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up-regulation of lysyl oxidase-like 2. J Cell Mol Med. 2016; 20(2): 342-50, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v9i3.647

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